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Cost-Effectiveness of
Cervical Cancer Screening Strategies:
Examples from Different World Regions
Jane J. Kim, Ph.D.
Sue J. Goldie, M.D., M.P.H.
Harvard School of Public Health
Boston, MA, USA
Cervical Cancer Control
• Public health success in countries with cytology (Pap smear)
screening programs where mortality has been reduced by 75%
• Public health failure in developing countries where ~90% of
all cervical cancer deaths occur
 infrastructure and technological expertise for cytology
programs not available
 three visits for screening, diagnosis, and treatment not
feasible
Overview of Decision-Analytic Methods
• Develop mathematical model of the natural history of
disease.
• Synthesize clinical and economic data from multiple sources
(clinical trials, cohort studies, national surveys, databases).
• Calibrate model to achieve the best fit to epidemiological
data; validate model by predicting outcomes consistent with
observations from independent data.
• “Simulate” different interventions to estimate consequences
(e.g., life-expectancy, quality of life, costs).
Objectives
• To develop and validate models of the natural history of
cervical cancer in developed and developing country
populations.
• To conduct formal cost-effectiveness analysis of
alternative cervical cancer screening strategies.
Example 1
Cost-Effectiveness of Management Strategies for
Atypical Squamous Cells of Undetermined
Significance in the United States*
Jane J. Kim, PhD; Thomas C. Wright, MD; Sue J. Goldie, MD, MPH
* JAMA (2002)
Introduction
• Cervical cancer control has been largely successful in
the U.S., where annual screening is recommended.
• More than 2 million U.S. women are diagnosed with an
equivocal result referred to as “atypical squamous cells
of undetermined significance” (ASCUS).
• The clinical response to an ASCUS result varies widely
and has been the subject of heated debate.
Cervical Cancer Model
Healthy
HPV
Low-grade
lesion
High-grade
lesion
Local
Cancer
Regional
Cancer
Distant
Cancer
Cervical Cancer Model
Healthy
HPV
Low-grade
lesion
High-grade
lesion
Local
Cancer
Regional
Cancer
Distant
Cancer
Cervical Cancer Model
Healthy
HPV
Low-grade
lesion
High-grade
lesion
Local
Cancer
Regional
Cancer
Distant
Cancer
Cervical Cancer Model
Healthy
HPV
Low-grade
lesion
High-grade
lesion
Local
Cancer
Regional
Cancer
Distant
Cancer
Cervical Cancer Model
Healthy
HPV
Low-grade
lesion
High-grade
lesion
Local
Cancer
Regional
Cancer
Distant
Cancer
Cervical Cancer Model
Healthy
HPV
Low-grade
lesion
High-grade
lesion
Local
Cancer
Regional
Cancer
Distant
Cancer
Cervical Cancer Model
Healthy
HPV
• Low-Risk
• High-Risk
Low-grade
lesion
High-grade
lesion
Local
Cancer
Regional
Cancer
Distant
Cancer
Predictive Validity (1)
30%
Model
Prevalence of HPV
25%
Published Data
20%
15%
10%
5%
0%
15-19
20-24
25-29
Age (year)
29-33
34-39
40-49
Prevalence of Low-Grade Lesions
Predictive Validity (2)
10%
9%
8%
Model
7%
Data
6%
5%
4%
3%
2%
1%
0%
25
35
45
Age (year)
55
65
75
Strategies
1. Ignore ASCUS result (least aggressive)
2. Immediate colposcopy (most aggressive)
3. Repeat Pap smear at 6-month intervals (most common)
4. Human Papillomavirus (HPV) DNA testing (new)
Routine Pap Smear Screening
Screening
Test
Liquid-based
Conventional
Sensitivity
(CIN 1)
Sensitivity Specificity
Cost
(CIN 2,3)
70%
80%
95%
$30
(55-90)
(60-95)
(92-98)
(17-45)
56%
64%
95%
$17
(50-70)
(55-75)
(92-98)
(13-30)
Incremental Cost-Effectiveness Ratio
Net increase in health care cost
Net gain in health effect
– measure of “value” for resources
– data for comparative analysis
Cost-Effectiveness Results
(2-year Liquid-Based Pap)
Costs
LE
C/E
C/E
Strategy
(US $)
(years)
($/YLS)
($/QALY)
No Screen
Ignore ASCUS
HPV Test
Repeat Paps
Colposcopy
210
1,420
1,710
1,820
1,870
28.6987
-----28.7874
13,700
12,300
28.7939 44,400
36,100
28.7937 dominated dominated
28.7941
905,300
667,300
Interpreting Cost-Effectiveness Results
The Commission on Macroeconomics and Health recently
defined interventions that have a cost-effectiveness ratio less
than the GDP per capita as very cost-effective.
Cost-Effectiveness Results
(2-year Liquid-Based Pap)
Costs
LE
C/E
C/E
Strategy
(US $)
(years)
($/YLS)
($/QALY)
No Screen
Ignore ASCUS
HPV Test
Repeat Paps
Colposcopy
210
1,420
1,710
1,820
1,870
28.6987
-----28.7874
13,700
12,300
28.7939 44,400
36,100
28.7937 dominated dominated
28.7941
905,300
667,300
Efficiency Frontier
HPV test
Liquid Pap, 5-yr
$20,300/YLS
Discounted Life Expectancy (years)
28.82
HPV test
Liquid Pap, 3-yr
$59,600/YLS
HPV test
Liquid Pap, 2-yr
$174,200/YLS
HPV test
Liquid Pap, 1-yr
$794,300/YLS
Repeat Pap
Liquid Pap, 1-yr
$1,846,000/YLS
HPV test
Conv Pap, 5-yr
$12,100/YLS
28.80
28.78
Ignore ASCUS
Conv Pap, 5-yr
$7,100/YLS
28.76
28.74
28.72
28.70
No Screening
28.68
$0
$500
$1,000
$1,500
$2,000
Discounted Lifetime Costs
$2,500
$3,000
$3,500
Conclusions
• A strategy of repeat Pap (the most common strategy) is
more costly and less effective than HPV testing.
• Immediate colposcopy (considered the most effective
strategy) is more costly but provides only hours of lifeexpectancy benefit compared with HPV testing.
• Cost-effectiveness ratios associated with HPV testing for
ASCUS in the context of every two- or three-year
screening is attractive compared with other well-accepted
public health interventions.
Example 2
Cost-Effectiveness of HPV DNA Testing
in the UK, the Netherlands,
France, and Italy*
Jane J. Kim, PhD; Thomas C. Wright, MD; Sue J. Goldie, MD, MPH
* J Natl Cancer Inst (2005)
Country-Specific Policies
UK
Netherlands
France
Italy
3, 5 years
5 years
3 years
3 years
Ages
(years)
20-65
30-60
25-65
25-65
Coverage
84%
80%
60%
70%
Equivocal
result
Repeat
Pap
Repeat
Pap
None
Colposcopy
Screening
Interval
Strategies
1. Pap smear throughout lifetime
HPV test to triage women with equivocal results
2. Pap smear until age 30
HPV test instead of Pap smear after 30
3. Pap smear until age 30
HPV test in combination with Pap smear after 30
Country-Specific Data
Sensitivity
Specificity
Cost*
Pap
58 - 80%
93 - 98%
$36 - 94
HPV Test
88 - 90%
91 - 95%
$47 - 121
Pap + HPV Test
94 - 96%
88 - 93%
$70 - 146
* All costs expressed in 2001 international dollars; includes lab, office visit,
patient time, and transportation.
Cost-Effectiveness Ratios*
Strategy**
UK
Netherlands
France
Italy
-
-
-
-
HPV Test as Triage
6,300
3,400
8,100
10,100
HPV Test Alone (>30)
19,800
21,800
24,200
38,100
HPV Test + Pap (>30)
49,300
25,300
38,900
45,800
Status Quo (by country)
* CE-ratios expressed in I$ per QALY-gained.
** All strategies assume same frequency as status quo policy.
Cost-Effectiveness Ratios*
Strategy**
UK
Netherlands
France
Italy
-
-
-
-
HPV Test as Triage
6,300
3,400
8,100
10,100
HPV Test Alone (>30)
19,800
21,800
24,200
38,100
HPV Test + Pap (>30)
49,300
25,300
38,900
45,800
Status Quo (by country)
* CE-ratios expressed in I$ per QALY-gained.
** All strategies assume same frequency as status quo policy.
Cost-Effectiveness Ratios*
Strategy**
UK
Netherlands
France
Italy
-
-
-
-
HPV Test as Triage
6,300
3,400
8,100
10,100
HPV Test Alone (>30)
19,800
21,800
24,200
38,100
HPV Test + Pap (>30)
49,300
25,300
38,900
45,800
GDP per capita
30,200
31,700
29,100
25,600
Status Quo (by country)
Conclusions
• Policies incorporating HPV testing (either for triage of
equivocal results or for primary screening in women >30)
will provide greater benefit than the status quo.
• At current screening frequencies of every 3 to 5 years, the
use of HPV testing as a primary screening test (alone or
combined with a Pap smear) has an attractive costeffectiveness ratio.
Example 3
Cost-Effectiveness of
Cervical Cancer Screening in
Kenya, India, Peru, South Africa, Thailand*
S. Goldie, L. Gaffikin, J. Goldhaber-Fiebert, A. Gordilla,
C. Levin, C. Mahe, T. Wright
Engender Health, International Agency for Research on Cancer, JHPIEGO Corporation, Pan
American Health Organization, Program for Appropriate Technology in Health
Sponsored by the Bill & Melinda Gates Foundation
* NEJM (2005)
Proposed Alternatives
• Simplify Pap Strategy
– eliminate diagnostic confirmation step (2nd visit)
• Visual Inspection Methods (VIA)
– acetic acid applied to cervix, inspected by naked eye
– no lab services required, provides immediate result
• HPV DNA testing
– test for high-risk HPV types in cervical smear
– minimal training and quality control constraints, self-collected
specimens are possible
Strategies
• Screening test: Pap, VIA, or HPV
• Number of clinical contacts: 1-visit, 2-visit, 3-visit
• Frequency: 1x, 2x, 3x, 5-year
• Optimal target age: 20 – 50 (5 year intervals)
Screening Test Performance
Screening Test
Pap smear
Visual inspection (VIA)
HPV DNA test
Sensitivity
Specificity
63%
94%
(33-90)
(75-98)
76%
84%
(56-90)
(64-98)
88%
93%
(58-95)
(77-97)
Screening Cost Components
S Africa
50
Kenya
40
Peru
30
Thailand
India
20
10
PV
H
p
Pa
VI
A
PV
H
p
Pa
VI
A
PV
H
p
Pa
VI
A
PV
H
p
Pa
VI
A
PV
H
Pa
p
0
VI
A
Component Cost (I$ 2000)
60
Screen Type/Country
Staff
Disposable Supplies
Equipment and Lab
Woman (Time)
Woman (Transport)
Results: Thailand
27.42
Life Expectancy (years)
27.40
27.38
27.36
27.34
No
Screening
27.32
27.30
$0
$20
$40
$60
$80
$100
Discounted Total Lifetime Cost (I$ 2000)
$120
$140
Results: Thailand
27.42
Life Expectancy (years)
27.40
27.38
1 Visit HPV, 1X
$170/YLS
27.36
1 Visit VIA, 1X
$109/YLS
27.34
No
Screening
27.32
27.30
$0
$20
$40
$60
$80
$100
Discounted Total Lifetime Cost (I$ 2000)
$120
$140
Results: Thailand
27.42
Life Expectancy (years)
27.40
27.38
1 Visit HPV, 1X
$170/YLS
27.36
29- 33% cancer reduction
1 Visit VIA, 1X
$109/YLS
27.34
No
Screening
27.32
27.30
$0
$20
$40
$60
$80
$100
Discounted Total Lifetime Cost (I$ 2000)
$120
$140
Results: Thailand
Life Expectancy (years)
27.42
27.40
1 Visit HPV, 2X
$310/YLS
27.38
1 Visit VIA, 2X
$277/YLS
45- 49% cancer reduction
1 Visit HPV, 1X
$170/YLS
27.36
1 Visit VIA, 1X
$109/YLS
27.34
No
Screening
27.32
27.30
$0
$20
$40
$60
$80
$100
Discounted Total Lifetime Cost (I$ 2000)
$120
$140
Results: Thailand
1 Visit HPV, 3X
$658/YLS
Life Expectancy (years)
27.42
27.40
1 Visit HPV, 2X
$310/YLS
27.38
1 Visit VIA, 2X
$277/YLS
60% cancer reduction
1 Visit HPV, 1X
$170/YLS
27.36
1 Visit VIA, 1X
$109/YLS
27.34
No
Screening
27.32
27.30
$0
$20
$40
$60
$80
$100
Discounted Total Lifetime Cost (I$ 2000)
$120
$140
Results: Thailand
1 Visit HPV, 3X
$658/YLS
Life Expectancy (years)
27.42
27.40
1 Visit HPV, 2X
$310/YLS
27.38
1 Visit VIA, 2X
$277/YLS
1-visit VIA
2-visit VIA
27.36
1 Visit HPV, 1X
$170/YLS
2-visit HPV
27.34
1 Visit VIA, 1X
$109/YLS
1-visit HPV
3-visit HPV
27.32
1x per lifetime
2-visit Pap
2x per lifetime
3-visit Pap
3x per lifetime
2-visit HPV/VIA
27.30
$0
$20
$40
$60
$80
$100
Discounted Total Lifetime Cost (I$ 2000)
$120
$140
CE Ratios* for Strategies on Efficient Frontier
Screening and treatment in a single visit
Strategy
India
Kenya
Peru
VIA, 1x lifetime
HPV, 1x lifetime
VIA, 2x lifetime
HPV, 2x lifetime
VIA, 3x lifetime
HPV, 3x lifetime
10
91
268
591
134
319
705
1,119
124
152
453
1,145
S.Africa Thailand
467
1,093
2,458
109
170
277
310
658
CE Ratios* for Strategies on Efficient Frontier
Screening and treatment in a single visit
Strategy
India
Kenya
Peru
VIA, 1x lifetime
HPV, 1x lifetime
VIA, 2x lifetime
HPV, 2x lifetime
VIA, 3x lifetime
HPV, 3x lifetime
GDP per capita
10
91
268
591
462
134
319
705
1,119
371
124
152
453
1,145
2,051
S.Africa Thailand
467
1,093
2,458
2,620
109
170
277
310
658
1,874
Summary of Results
• Previous recommendations: Pap smear 3x per lifetime at
ten year intervals (e.g., age 20, 30, 40)
• Pap smears are consistently both less effective and less
cost-effective than VIA and HPV testing.
• Optimal age to screen is between 35-45 years of age;
optimal interval is every 5 years, not every 10 years.
• Cervical cancer incidence could decrease up to ~30-50%
with 1 or 2 screenings.
Reduction in Lifetime Risk of Cancer
100%
1-year Cytology (Liquid)
>$1 million per YLS
(US)
2-year Cytology (Liquid)
$174,200-$452,600 per YLS
(US)
2-year Cytology
$34,500-$56,400 per YLS
(US)
90%
80%
3- and 5-year Cytology
$6,800-$25,600 per YLS
(UK, Netherlands, France, Italy)
70%
60%
50%
3x Lifetime HPV
$590-$2,500 per YLS
(India, Kenya, Peru, South Africa, Thailand)
40%
30%
1x Lifetime VIA
$110-$130 per YLS
(India, Kenya, Peru, Thailand)
20%
10%
0%
0
500
1000
1500
2000
2500
Total Lifetime Costs Per Woman ($)
3000
3500
4000
Key Themes
• For countries with existing screening programs, substitution
of annual Pap smears with more sensitive tests (i.e., HPV
test or liquid-based Pap) without modification of the
screening interval will not be cost-effective;
• These options in the context of every 2-3 year screening,
would provide comparable or better cancer protection than
the status quo and would be reasonably cost-effective.
• For countries with limited resources, screening efforts
should target women age 35 or older, and efforts should
focus on attaining high coverage of single lifetime
screening before increasing the frequency of screening.